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THYROID AXIS INHIBITION IN XENOPUS LAEVIS: DEVELOPMENT OF AN AMPHIBIAN-BASED SCREENING ASSAY FOR THYROID DISRUPTION
Citation:
Tietge, J E., G W. Holcombe, K. M. Flynn, J J. Korte, R C. Kolanczyk, P A. Kosian, AND S J. Degitz. THYROID AXIS INHIBITION IN XENOPUS LAEVIS: DEVELOPMENT OF AN AMPHIBIAN-BASED SCREENING ASSAY FOR THYROID DISRUPTION. Presented at Endocrine Disruptor Contaminant (EDC) Program Review Workshop, Research Triangle Park, NC, October 29-31, 2002.
Description:
In response to the initial EDSTAC recommendations, research was conducted on the development of a Xenopus laevis based tail resorption assay for evaluating thyroid axis disruption. These experiments highlighted key limitations associated with reliance on tail resorption as a measure of anti/thyroid activity. The most critical being that tail tissue of tadpoles in metamorphic climax are insensitive to perturbation by agonists/antagonist. To improve on the initial proposal we have conducted experiments comparing the sensitivity of pre-metamorphic (stage 51) and pro-metamorphic (stage 54) tadpoles to the model thyroid axis antagonists methimazole, 6-propythiouracil perchlorate and iopanoic acid. Tadpoles were exposed for a 2 wk period, and developmental stage, thyroid size, and histology were examined at 1 and 2 wks after exposure. The changes were characterized as reduced colloid, glandular hypertrophy, and cellular hyperplasia. Treatment failed to affect growth, even in tadpoles which experienced significant metamorphic inhibition. As determined from these endpoints, there were only minor differences in sensitivity observed among the 2 stages examined. Iopanoic acid, a type II deiodinase inhibitor, surprisingly stimulated metamorphosis. These results indicate that tadpoles in the early stages of metamorphosis are sensitive to thyroid axis inhibition and that development of a short term, diagnostic amphibian-based thyroid screening assay shows considerable promise. This abstract does not necessarily reflect EPA policy.